Chromosome-level reference genome and resequencing of 322 accessions reveal evolution, genomic imprint and key agronomic traits in adzuki bean.

Adzuki bean (Vigna angularis) is an important legume crop cultivated in over 30 countries worldwide. We developed a high-quality chromosome-level reference genome of adzuki bean cultivar Jingnong6 by combining PacBio Sequel long-read sequencing with short-read and Hi-C technologies. The assembled genome covers 97.8% of the adzuki bean genome with a contig N50 of approximately 16 Mb and a total of 32 738 protein-coding genes. We also generated a comprehensive genome variation map of adzuki bean by whole-genome resequencing (WGRS) of 322 diverse adzuki beans accessions including both wild and cultivated. Furthermore, we have conducted comparative genomics and a genome-wide association study (GWAS) on key agricultural traits to investigate the evolution and domestication. GWAS identified several candidate genes, including VaCycA3;1, VaHB15, VaANR1 and VaBm, that exhibited significant associations with domestication traits. Furthermore, we conducted functional analyses on the roles of VaANR1 and VaBm in regulating seed coat colour. We provided evidence for the highest genetic diversity of wild adzuki (Vigna angularis var. nipponensis) in China with the presence of the most original wild adzuki bean, and the occurrence of domestication process facilitating transition from wild to cultigen. The present study elucidates the genetic basis of adzuki bean domestication traits and provides crucial genomic resources to support future breeding efforts in adzuki bean.

Generalizable transcriptome-based tumor malignant level evaluation and molecular subtyping towards precision oncology.

In cancer treatment, therapeutic strategies that integrate tumor-specific characteristics (i.e., precision oncology) are widely implemented to provide clinical benefits for cancer patients. Here, through in-depth integration of tumor transcriptome and patients' prognoses across cancers, we investigated dysregulated and prognosis-associated genes and catalogued such important genes in a cancer type-dependent manner. Utilizing the expression matrices of these genes, we built models to quantitatively evaluate the malignant levels of tumors across cancers, which could add value to the clinical staging system for improved prediction of patients' survival. Furthermore, we performed a transcriptome-based molecular subtyping on hepatocellular carcinoma, which revealed three subtypes with significantly diversified clinical outcomes, mutation landscapes, immune microenvironment, and dysregulated pathways. As tumor transcriptome was commonly profiled in clinical practice with low experimental complexity and cost, this work proposed easy-to-perform approaches for practical clinical promotion towards better healthcare and precision oncology of cancer patients.

Comparative performance of contact plate metod and swab method for surface microbial contamination on medical fabrics.

BACKGROUND: The contact plate method is widely accepted and used in various fields where hygiene and contamination levels are crucial. Evidence regarding the applicability of the contact plate method for sampling fabric microbial contamination levels in real medical environments was limited. This study aimed to assess the applicability of the contact plate method for detecting microbial contamination on medical fabrics in a real healthcare environment, thereby providing a benchmark for fabric microbial sampling methods. METHODS: In a level three obstetrics ward of a hospital, twenty-four privacy curtains adjacent to patient beds were selected for this study. The contact plate and swab method were used to collect microbial samples from the privacy curtains on the 1st, 7th, 14th, and 28th days after they were hung. The total colony count on each privacy curtain surface was calculated, and microbial identification was performed. RESULTS: After excluding the effects of time, room type, and curtain location on the detected microbial load, the linear mixed-effects model analysis showed that contact plate method yielded lower colony counts compared to swab method (P < 0.001). However, the contact plate method isolated more microbial species than swab method (P < 0.001). 291 pathogenic strains were isolated using the contact plate method and 133 pathogenic strains were isolated via the swab method. There was no difference between the two sampling methods in the detection of gram-negative bacteria (P = 0.089). Furthermore, the microbial load on curtains in double-occupancy rooms was lower than those in triple-occupancy rooms (P = 0.021), and the microbial load on curtains near windows was lower than that near doors (P = 0.004). CONCLUSION: Contact plate method is superior to swab method in strain isolation. Swab method is more suitable for evaluating the bacterial contamination of fabrics.

TS-LCD: Two-Stage Loop-Closure Detection Based on Heterogeneous Data Fusion.

Loop-closure detection plays a pivotal role in simultaneous localization and mapping (SLAM). It serves to minimize cumulative errors and ensure the overall consistency of the generated map. This paper introduces a multi-sensor fusion-based loop-closure detection scheme (TS-LCD) to address the challenges of low robustness and inaccurate loop-closure detection encountered in single-sensor systems under varying lighting conditions and structurally similar environments. Our method comprises two innovative components: a timestamp synchronization method based on data processing and interpolation, and a two-order loop-closure detection scheme based on the fusion validation of visual and laser loops. Experimental results on the publicly available KITTI dataset reveal that the proposed method outperforms baseline algorithms, achieving a significant average reduction of 2.76% in the trajectory error (TE) and a notable decrease of 1.381 m per 100 m in the relative error (RE). Furthermore, it boosts loop-closure detection efficiency by an average of 15.5%, thereby effectively enhancing the positioning accuracy of odometry.

Comparative Analysis of Sampling Methods for Assessing Bacterial Contamination on Hospital Partition Curtains: Moistened Swabs versus RODAC Agar Plates.

BACKGROUND Partition curtains are one of the main sources of nosocomial infection in the hospital environment. However, there are no unified standards for monitoring medical textiles across different countries or regions. This study aimed to investigate the accuracy of 2 different sampling methods - swabbing vs RODAC (replicate organism detection and counting) agar plate - in terms of detection of bacterial contamination, and their suitability as monitoring methods for partition curtains and other medical textiles. MATERIAL AND METHODS A total of 24 partition curtains were selected by stratified random sampling. The swabbing technique and RODAC agar plates were the chosen sampling methods. The number of colony-forming units was calculated and colony morphologies and strains on the plates were observed and identified after culturing. RESULTS A total of 192 samples were collected. Of them, 161 pathogenic strains were isolated via the swabbing technique and 309 pathogenic strains were isolated using the RODAC agar plates. The swabbing technique had a higher proportion for gram-positive bacteria (P=0.0004), while RODAC agar plates had a higher proportion for gram-negative bacteria (P=0.72). The detection of bacterial contamination rates using the swabbing technique was superior to that of the RODAC agar plate method (P<0.001). CONCLUSIONS The swabbing technique offers more advantages in terms of detection of bacterial contamination rates and gram-positive bacteria, while the RODAC agar plate is more sensitive for detection of gram-negative bacteria.

Berberine Regulates GPX4 to Inhibit Ferroptosis of Islet ß Cells.

Ferroptosis, as a kind of non-apoptotic cell death, is involved in the pathogenesis of type 1 diabetes mellitus (T1DM). Islet B cells mainly produce insulin that is used to treat diabetes. Berberine (BBR) can ameliorate type 2 diabetes and insulin resistance in many ways. However, a few clues concerning the mechanism of BBR regulating ferroptosis of islet ß cells in T1DM have been detected so far. We measured the effects of BBR and GPX4 on islet ß cell viability and proliferation by MTT and colony formation assays. Western blot and qRT-PCR were utilized to examine GPX4 expression in islet ß cells with distinct treatments. The influence of BBR and GPX4 on ferroptosis of islet ß cells was investigated by evaluating the content of Fe2+ and reactive oxygen species (ROS) in cells. The mechanism of BBR targeting GPX4 to inhibit ferroptosis of islet ß cells was further revealed by the rescue experiment. Our results showed that BBR and overexpression of GPX4 could notably accelerate cell viability and the proliferative abilities of islet ß cells. Moreover, BBR stimulated GPX4 expression to reduce the content of Fe2+ and ROS, thereby repressing the ferroptosis of islet ß cells, which functioned similarly as ferroptosis inhibitor Fer-1. In conclusion, BBR suppressed ferroptosis of islet ß cells via promoting GPX4 expression, providing new insights into the mechanism of BBR for islet ß cells.

Endocrine, genetic, and microbiome nexus of obesity and potential role of postbiotics: a narrative review.

Obesity is a public health crisis, presenting a huge burden on health care and the economic system in both developed and developing countries. According to the WHO's latest report on obesity, 39% of adults of age 18 and above are obese, with an increase of 18% compared to the last few decades. Metabolic energy imbalance due to contemporary lifestyle, changes in gut microbiota, hormonal imbalance, inherent genetics, and epigenetics is a major contributory factor to this crisis. Multiple studies have shown that probiotics and their metabolites (postbiotics) supplementation have an effect on obesity-related effects in vitro, in vivo, and in human clinical investigations. Postbiotics such as the SCFAs suppress obesity by regulating metabolic hormones such as GLP-1, and PPY thus reducing feed intake and suppressing appetite. Furthermore, muramyl di-peptides, bacteriocins, and LPS have been tested against obesity and yielded promising results in both human and mice studies. These insights provide an overview of targetable pharmacological sites and explore new opportunities for the safer use of postbiotics against obesity in the future.

Identification of miRNA-mRNA-TF regulatory networks in peripheral blood mononuclear cells of type 1 diabetes.

BACKGROUND: Type 1 diabetes (T1D) is a T lymphocyte-mediated and B lymphocyte-assisted autoimmune disease. We aimed to identify abnormally expressed genes in peripheral blood mononuclear cells (PBMCs) of T1D and explore their possible molecular regulatory network. METHODS: Expression datasets were downloaded from the Gene Expression Omnibus (GEO) database. Then, the differentially expressed genes (DEGs) and differentially expressed miRNAs (DEmiRNAs) were identified, and functional enrichment and immune cell infiltration analysis were performed. The starBase, miRTarBase, TarBase, JASPAR, ENCODE, and TRRUST databases constructed the miRNA-mRNA-TF regulatory network. The ROC curves were plotted to evaluate the sensitivity and specificity of miRNAs and mRNAs. RESULT: A total of 216 DEGs directly or indirectly related to type I diabetes mellitus, natural killer cell-mediated cytotoxicity, Th1, and Th2 cell differentiation, and the IL-17 and TNF signaling pathways were obtained. The miRNA-mRNA-TF network indicates that miR-320a and SOX5 are the only miRNAs and TFs that both target ADM and RRAGD. The ROC curves showed that ADM (0.9375), RRAGD (0.8958), and hsa-mir-320a (0.9417) had high accuracy in T1D diagnosis. CONCLUSION: The constructed regulatory networks, including miR-320a/ADM/SOX5 and miR-320a/RRAGD/SOX5, may provide new insight into the mechanisms of development and progression in T1D.

Biosynthesis of a New Fusaoctaxin Virulence Factor in Fusarium graminearum Relies on a Distinct Path To Form a Guanidinoacetyl Starter Unit Priming Nonribosomal Octapeptidyl Assembly.

Fusarium graminearum is a pathogenic fungus causing huge economic losses worldwide via crop infection leading to yield reduction and grain contamination. The process through which the fungal invasion occurs remains poorly understood. We recently characterized fusaoctaxin A in F. graminearum, where this octapeptide virulence factor results from an assembly line encoded in fg3_54, a gene cluster proved to be involved in fungal pathogenicity and host adaptation. Focusing on genes in this cluster that are related to fungal invasiveness but not to the biosynthesis of fusaoctaxin A, we here report the identification and characterization of fusaoctaxin B, a new octapeptide virulence factor with comparable activity in wheat infection. Fusaoctaxin B differs from fusaoctaxin A at the N-terminus by possessing a guanidinoacetic acid (GAA) unit, formation of which depends on the combined activities of the protein products of fgm1-3. Fgm1 is a cytochrome P450 protein that oxygenates l-Arg to 4(R)-hydroxyl-l-Arg in a regio- and stereoselective manner. Then, Cß-Cγ bond cleavage proceeds in the presence of Fgm3, a pyridoxal-5'-phosphate-dependent lyase, giving guanidinoacetaldehyde and l-Ala. Rather than being directly oxidized to GAA, the guanidine-containing aldehyde undergoes spontaneous cyclization and subsequent enzymatic dehydrogenation to provide glycociamidine, which is linearized by Fgm2, a metallo-dependent amidohydrolase. The GAA path in F. graminearum is distinct from that previously known to involve l-Arg:l-Gly aminidotransferase activity. To provide this nonproteinogenic starter unit that primes nonribosomal octapeptidyl assembly, F. graminearum employs new chemistry to process l-Arg through inert C-H bond activation, selective C-C bond cleavage, cyclization-based alcohol dehydrogenation, and amidohydrolysis-associated linearization.

Correction: Characterization of a carboxyl methyltransferase in Fusarium graminearum provides insights into the biosynthesis of fusarin A.

Correction for 'Characterization of a carboxyl methyltransferase in Fusarium graminearum provides insights into the biosynthesis of fusarin A' by Qian Yang et al., Org. Biomol. Chem., 2021, DOI: 10.1039/d1ob01010g.

Characterization of a carboxyl methyltransferase in Fusarium graminearum provides insights into the biosynthesis of fusarin A.

Fusarium graminearum is a major fungal pathogen that causes a series of devastating crop diseases by producing a variety of mycotoxins. Fusarins are a class of polyketide-nonribosomal peptide hybrids. In Fusarium mycotoxins, a variable 2-pyrrolidone ring conjugates with a polyene chain substituted with a methyl ester moiety. The enzymatic route through which fusarin A, a major member of the fusarin family with a characteristic tetrohydrofuran-coupled pyrrolidone ring, is formed in F. graminearum has not been established. By targeting the final step in the biosynthesis of fusarin A, we report here an S-adenosyl methionine-dependent carboxyl methyltransferase responsible for the formation of the methyl ester moiety by in vivo gene inactivation, isolation and characterization of a key fusarin intermediate, and in vitro biochemical characterization. Related findings provide insights into the poorly understood biosynthetic pathway of fusarin A. Additionally, bioactivity assays demonstrate that the methyl ester is necessary for fusarin cytotoxicity.

Sini decoction ameliorates interrelated lung injury in septic mice by modulating the composition of gut microbiota.

Our work used cecal ligation and puncture (CLP) mice model and 16S rDNA sequencing to explore whether the therapeutic mechanism of Sini Decoction (SND) on sepsis was related to the intestinal flora currently of concern. Twenty-four hours after surgery, tissues and serum from three groups (Control, CLP and CLP + SND) were collected for further analysis and colon contents were isolated for 16S rDNA analysis. Mortality, histological examination and inflammatory cytokines levels confirmed that the sepsis model was induced successfully and resulted in serious pathological damage, while all of these could be reversed by SND. In intestinal flora analysis, the microbial richness and abundance were recovered after SND treatment. Furthermore, at the phylum level, the abundance of Proteobacteria showed drastic increase after CLP. Similarly, CLP surgery significantly disrupted the balance of intestinal flora, with a huge increase of Escherichia-Shigella, a Gram-negative genus that might release lipopolysaccharide (LPS) and other genera. And these shifts could be defused by SND, indicating its function of regulating gut microbiota. This study demonstrates that SND could ameliorate the symptoms and pathology associated with sepsis in CLP model via modulating the flora in intestinal tract, which enriches a possible mechanism of SND's therapeutic effect.

2,4,5-Trichloro-6-((2,4,6-trichlorophenyl)amino)isophthalonitrile, Exerts Anti-bladder Activities through IGF-1R/STAT3 Signaling.

2,4,5-Trichloro-6-((2,4,6-trichlorophenyl)amino)isophthalonitrile (SYD007) is a small molecule compound that was synthesized according to the structure of diarylamine. In this study, we evaluated the anti-bladder activities of SYD007, and determined its cytotoxic mechanism. We found that SYD007 exerted cytotoxicity to bladder cancer cells. Furthermore, SYD007 induced bladder cancer cell early apoptosis and arrested cell cycle. Mechanistically, SYD007 suppressed phosphorylated signal transducer and activator of transcription 3 (p-STAT3) (Tyr705) level in parallel with increases of p-extracellular signal-regulated kinase (ERK) and p-AKT. SYD007 significantly inhibited insulin-like growth factor 1 (IGF-1)-induced STAT3 activation through down-regulation of total IGF-1R level. No dramatic changes in IGF-1R mRNA levels were observed in SYD007-treated cells, suggesting that SYD007 acted primarily at a posttranscriptional level. Using molecular docking analysis, SYD007 was identified as an IGF-1R inhibitor. In summary, we reported that SYD007 exerted anti-bladder activities, and these effects were partially due to inhibition of IGF-1R/STAT3 signaling.

Influence of Oxygen Vacancy Behaviors in Cooling Process on Semiconductor Gas Sensors: A Numerical Analysis.

The influence of oxygen vacancy behaviors during a cooling process in semiconductor gas sensors is discussed by the numerical analysis method based on the gradient-distributed oxygen vacancy model. A diffusion equation is established to describe the behaviors of oxygen vacancies, which follows the effects of diffusion and exclusion in the cooling process. Numerical analysis is introduced to find the accurate solutions of the diffusion equation. The solutions illustrate the oxygen vacancy distribution profiles, which are dependent on the cooling rate as well as the temperature interval of the cooling process. The gas-sensing characteristics of reduced resistance and response are calculated. Both of them, together with oxygen vacancy distribution, show the grain size effects and the re-annealing effect. It is found that the properties of gas sensors can be controlled or adjusted by the designed cooling process. The proposed model provides a possibility for sensor characteristics simulations, which may be beneficial for the design of gas sensors. A quantitative interpretation on the gas-sensing mechanism of semiconductors has been contributed.

Systematic biases in reference-based plasma cell-free DNA fragmentomic profiling.

Plasma cell-free DNA (cfDNA) fragmentation patterns are emerging directions in cancer liquid biopsy with high translational significance. Conventionally, the cfDNA sequencing reads are aligned to a reference genome to extract their fragmentomic features. In this study, through cfDNA fragmentomics profiling using different reference genomes on the same datasets in parallel, we report systematic biases in such conventional reference-based approaches. The biases in cfDNA fragmentomic features vary among races in a sample-dependent manner and therefore might adversely affect the performances of cancer diagnosis assays across multiple clinical centers. In addition, to circumvent the analytical biases, we develop Freefly, a reference-free approach for cfDNA fragmentomics profiling. Freefly runs ∼60-fold faster than the conventional reference-based approach while generating highly consistent results. Moreover, cfDNA fragmentomic features reported by Freefly can be directly used for cancer diagnosis. Hence, Freefly possesses translational merit toward the rapid and unbiased measurement of cfDNA fragmentomics.

Innovation in Boundary-Spanning Technology M&A: A Fuzzy-Set Analysis of Diversity Dynamics.

The growing literature on organizational innovation has drawn attention from net effect and contingent effect of diversity-related factors in the context of top management teams (TMTs) to their complementarity and interaction in the form of configurations. In post-boundary-spanning technology mergers & acquisitions (M&A), the integration between multi-boundary knowledge and resources necessitates effective communication and cooperation within TMTs that display heterogeneous attributes. Therefore, this study integrates two popular theoretical perspectives from the diversity literature (social categorization perspectives and information/decision-making perspectives) in order to explore the configurational patterns of factors stimulating innovation in boundary-spanning technology M&A (BTM&A). In accordance with this theoretical objective, this study adopts fuzzy-set qualitative comparative analysis for the purpose of examining the complex combinations of five antecedent conditions (functional experience diversity, boundary-spanning experience diversity, faultline strength, number of subgroups, and subgroup balance) based on a BTM&A sample of firms in the Chinese A-share market during the period 2007-2018. Findings from this analysis indicates four configurations of diversity-related factors (the dominated multiple diversities; the non-aligned multiple diversities; the balanced similarity; and the aligned single diversity) which lead to superior innovation in BTM&A. This study fills a gap in the literature vis-à-vis the causes of innovation in BTM&A and provides novel insights for management practitioners to take appropriate countermeasures with regard to TMT diversity.

Rhein ameliorates septic lung injury and intervenes in macrophage metabolic reprogramming in the inflammatory state by Sirtuin 1.

AIMS: Sepsis is an organ dysfunction syndrome caused by the maladjustment of response to infection. Acute lung injury (ALI) appears the earliest, with urgent onset and limited treatments. Previous pharmacological studies have found that rhein (RH), an active ingredient rich in rhubarb, has multiple pharmacological activities such as anti-inflammatory, anti-infection and metabolic regulation. This research aimed to explore whether RH alleviates septic acute lung injury and probe possible mechanisms. MAIN METHODS: In this study, the septic ALI mouse model was established by cecal ligation and perforation (CLP). LPS-induced RAW264.7 model was selected to further explore the protective mechanism of RH. H&E staining, Western blot, qRT-PCR, and 1H NMR analysis were used to verify the protective effect of RH on ALI in vivo and vitro. KEY FINDINGS: RH could relieve pathological lung injury and pulmonary edema, reduce the serum LPS and inhibit inflammatory response in CLP mice. Further studies displayed that RH affected the metabolism in vivo, with significant changes in serum and lung metabolomics. In vitro results demonstrated that RH inhibited the expression of inflammatory mediators and factors in macrophages by affecting metabolic reprogramming and upregulating the expression of Sirtuin 1. SIGNIFICANCE: RH improved the overall metabolic condition of sepsis mice by up-regulating and activating SIRT1, and inhibited the over activation of macrophages by regulating metabolism. These findings reveal the therapeutic mechanism of RH on sepsis ALI from the perspective of metabolism.

Sinomenine ameliorates septic acute lung injury in mice by modulating gut homeostasis via aryl hydrocarbon receptor/Nrf2 pathway.

Sepsis is a systemic inflammatory response syndrome caused by a host's immune response to infection. Acute lung injury (ALI) is one of the most common complications of sepsis with high mortality and morbidity. Recent evidence demonstrated that the 'gut-lung axis' was related to the progression of septic acute lung injury, which regarded gut microbiota and intestinal barrier as two critical factors correlated with acute lung injury. Sinomenine is an isoquinoline alkaloid component extracted from Sinomenium acutum Rehd，et Wils, which has been already reported to have significant anti-inflammatory, immunosuppressive, and anti-arthritis properties. In this research, we observed that sinomenine could repair the lung injury and alleviate inflammatory response induced by cecum ligation and puncture (CLP). Illumine sequencing of 16S rDNA revealed that sinomenine could improve the richness of gut microbiota and modulate the composition of intestinal flora in cecum ligation and puncture mice. Meanwhile, sinomenine could reduce the colon pathological damage and improve the intestine barrier integrity in cecum ligation and puncture mice. We also found that the molecular mechanism of sinomenine's protective effect on intestinal tract was related to the activation of aryl hydrocarbon receptor/nuclear factor erythroid-2 related factor 2（Nrf2）pathway both in vivo and vitro experiments. Collectively, the prevention of septic acute lung injury by sinomenine might be mediated by modulating gut microbiota and restoring intestinal barrier via aryl hydrocarbon receptor/Nrf2-dependent pathway.

HOXC11 positively regulates the long non-coding RNA HOTAIR and is associated with poor prognosis in colon adenocarcinoma.

Colorectal cancer ranks third in terms of incidence and second in terms of mortality worldwide. The homeobox transcript antisense intergenic RNA (HOTAIR), which was found to be located on the antisense chain of the homeobox C (HOXC) gene cluster, is a long non-coding RNA involved in multiple types of tumors. The role of HOXC11 in tumors remains unclear. Reverse transcription-quantitative PCR was performed to detect the expression level of HOXC11 in colon adenocarcinoma. Cell proliferation and invasion were assessed. RNase protection assay was used to test the possibility of RNA duplex formation. The increased expression and co-expression trend of HOXC11 and HOTAIR were identified in multiple types of cancer from The Cancer Genome Atlas and the results were validated in 12 colon adenocarcinoma and paired non-tumor tissue samples. The expression of HOXC11 and HOTAIR was found to be associated with poor prognosis in colon adenocarcinoma and kidney renal clear cell carcinoma. Furthermore, HOXC11 was found to positively regulate HOTAIR by RNA duplex formation and promoted the proliferation and invasion of colon adenocarcinoma cells.

Unraveling the dynamic importance of county-level features in trajectory of COVID-19.

The objective of this study was to investigate the importance of multiple county-level features in the trajectory of COVID-19. We examined feature importance across 2787 counties in the United States using data-driven machine learning models. Existing mathematical models of disease spread usually focused on the case prediction with different infection rates without incorporating multiple heterogeneous features that could impact the spatial and temporal trajectory of COVID-19. Recognizing this, we trained a data-driven model using 23 features representing six key influencing factors affecting the pandemic spread: social demographics of counties, population activities, mobility within the counties, movement across counties, disease attributes, and social network structure. Also, we categorized counties into multiple groups according to their population densities, and we divided the trajectory of COVID-19 into three stages: the outbreak stage, the social distancing stage, and the reopening stage. The study aimed to answer two research questions: (1) The extent to which the importance of heterogeneous features evolved at different stages; (2) The extent to which the importance of heterogeneous features varied across counties with different characteristics. We fitted a set of random forest models to determine weekly feature importance. The results showed that: (1) Social demographic features, such as gross domestic product, population density, and minority status maintained high-importance features throughout stages of COVID-19 across 2787 studied counties; (2) Within-county mobility features had the highest importance in counties with higher population densities; (3) The feature reflecting the social network structure (Facebook, social connectedness index), had higher importance for counties with higher population densities. The results showed that the data-driven machine learning models could provide important insights to inform policymakers regarding feature importance for counties with various population densities and at different stages of a pandemic life cycle.